Azithrom

Each film-coated tablet contains: Azithromycin 500 mg.

Pharmacology: Pharmacokinetics: Azithromycin given orally is rapidly absorbed and about 40% bioavailable. Absorption from capsules, but not tablets or suspension, is reduced by food. Peak plasma concentrations occur 2 to 3 hours after an oral dose and 1 to 2 hours after intravenous dosage. Azithromycin is extensively distributed into the tissues, and tissue concentrations subsequently remain much higher than those in the blood; in contrast to most other antibacterials, plasma concentrations are therefore of little diffusion into the Cerebrospinal fluid when meninges are not inflamed. Data from animal studies indicate that Azithromycin crosses the placenta. Small amounts of Azithromycin are demethylated in the liver, and it is excreted in bile mainly as unchanged drug and a number of inactive metabolites have also been detected. About 6% of an oral dose (representing about 20% of the amount in the amount in the systemic circulation) is excreted in the urine. The terminal elimination half-life is about 68 hours.

Azithromycin is used in the treatment of respiratory-tract infections (including otitis media), in skin and soft-tissue infections, and in uncomplicated genital infections. It may also be used for the prophylaxis, and as a component of regimens in the treatment of Mycobacterium avium complex (MAC) infections. It is used in some countries for the prophylaxis of endocarditis in at risk patients unable to take penicillin. It is also used in the management of trachoma and typhoid.

The usual oral adult dose is 500 mg as a single dose daily for 3 days.
Alternatively, an initial dose of 500 mg may be followed by 250 mg daily for a further 4 days.
For uncomplicated genital infections caused by Chlamydia trachomatis and for chancroid, 1 g of Azithromycin is given as a single dose. A single dose of 2 g has been given for uncomplicated gonorrhoea.
For the treatment of granuloma inguinale, an initial dose of 1 g followed by 500 mg daily may be given, or 1 g may be given once a week for at least 3 weeks, until all lesions have completely healed.
For prophylaxis of disseminated MAC infections, Azithromycin 1.2 g may be given once weekly. For treatment or secondary prophylaxis, 500 mg once daily should be given with other antimycobacterials.

Patients with known hypersensitivity to Azithromycin, erythromycin, any other macrolide or ketolide antibiotic, or to any component of this product.

Azithromycin products may cause longer QT intervals resulting to cardiovascular death.

Licensed product information states that Azithromycin should be used with caution in patients with hepatic or renal impairment. It should not be given to those with severe hepatic impairment as safety has not been established. Although plasma concentrations may be increased in renal impairment dosage adjustment is not usually required.

Gastrointestinal disturbances are the most frequent adverse effect of Azithromycin but are usually mild and less frequent than with erythromycin. Headache, somnolence and taste disturbances may occur. Severe hypersensitivity reactions occur rarely but may be prolonged. Thrombocytopenia and mild transient neutropenia have been rarely reported in patients receiving Azithromycin. Pain and inflammation may occur at the site of intravenous infusions particularly at high concentrations.

Antacid: Giving Azithromycin with antacids containing aluminum or magnesium salts can reduce the rate, but not the extent, of its absorption; Azithromycin should be given at least 1 hour before or 2 hours after the antacid.
Fluconazole: Co-administration of a single dose of 1.2 g Azithromycin did not alter the pharmacokinetics of a single dose of 800 mg fluconazole, however, a clinically insignificant decrease in C_max (18%) of Azithromycin was observed.
Nelfinavir: Co-administration of Azithromycin (1.2 g) and nelfinavir at steady state (750 mg three times daily) resulted in increased Azithromycin concentrations. No clinically significant adverse effects were observed and no dose adjustment is required.
Rifabutin: Co-administration of Azithromycin and rifabutin did not affect the serum concentrations of either drug. Neutropenia was observed in subjects receiving concomitant treatment of Azithromycin and rifabutin. Although neutropenia has been associated with the use of rifabutin, a causal relationship to combination with Azithromycin has not been established.
Terfenadine: Pharmacokinetic studies have reported no evidence of an interaction between Azithromycin and terfenadine. There have been rare cases reported where possibility of such an interaction could not be entirely excluded; however there was no specific evidence that such interaction had occurred.
Cimetidine: In a pharmacokinetic study investigating the effects of single dose of cimetidine, given 2 hours before Azithromycin, on the pharmacokinetics of Azithromycin, no alteration of Azithromycin pharmacokinetics was seen.
Ergotamine derivatives: Due to the theoretical possibility of ergotism, the concurrent use of Azithromycin with ergot derivatives is not recommended.
Digoxin: It is known that some macrolide antibiotics limit the metabolism of digoxin (in the gut). In patients treated concomitantly with Azithromycin and digoxin, the possibility of increased digoxin levels should be borne in mind, and digoxin levels monitored.
Coumarin-type Oral Anticoagulants: In a pharmacokinetic interaction study, Azithromycin did not alter the anticoagulant effect of a single 15 mg dose of warfarin administered to healthy volunteers. There have been reports received in the post-marketing period of potentiated anticoagulation subsequent to co-administration of Azithromycin and coumarin-type oral anticoagulant. Although a causal relationship has not been established, consideration should be given to the frequency of monitoring prothrombin time when Azithromycin is used in patients receiving coumarin-type oral anticoagulants.
Cyclosporin: In a pharmacokinetic study with healthy volunteers that were administered a 500 mg/day oral dose Azithromycin for 3 days and were then administered a single 10 mg/kg oral dose of cyclosporine, the resulting cyclosporine C_max and AUC_0-5 were found to be significantly elevated. Consequently, caution should be exercised before considering concurrent administration of these drugs. Cyclosporine levels should be monitored and the dose adjusted accordingly.
Theophylline: There is no evidence of a clinically significant pharmacokinetic interaction when Azithromycin and theophylline are co-administered to healthy volunteers. As interactions of other macrolides with theophylline have been reported, alertness to signs that indicate a rise in theophylline levels is advised.
Trimethoprim/Sulfamethoxazole: Co-administration of trimethoprim/sulfamethoxazole (160 mg/800 mg) for 7 days with Azithromycin 1.2 g on day 7 had no significant effect on peak concentrations total exposure or urinary excretion of either trimethoprim or sulfamethoxazole. Azithromycin serum concentrations were similar to those seen in other studies.
Zidovudine: Single 1 g dose and multiple 1.2 g or 600 mg dose of Azithromycin had little effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolite. However, co-administration of Azithromycin increased the concentrations of phosphorylated zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells. The clinical significance of this finding is unclear, but it may be of benefit to patients. Azithromycin does not interact significantly with the hepatic cytochrome P450 system. It is not believed to undergo the pharmacokinetic drug interactions as seen with erythromycin and other macrolides. Hepatic cytochrome P450 induction or inactivation via cytochrome-metabolite complex does not occur with Azithromycin.
Astemizole, Alfentanil: There are no known data on interactions with astemizole or alfentanil. Caution is advised in the co-administration of these macrolides with Azithromycin because of the known enhancing effect of these medicines when used concurrently with the macrolide antibiotic erythromycin.
Atorvastatin: Co-administration of atorvastatin (10 mg daily) and Azithromycin (500 mg daily) did not alter the plasma concentrations of atorvastatin (based on a HMG CoA-reductase inhibition assay).
Carbamazepine: In a pharmacokinetic interaction study in healthy volunteers, no significant effect was observed on the plasma levels of carbamazepine or its active metabolite in patients receiving concomitant Azithromycin.
Cisapride: Cisapride is metabolized in the liver by the enzyme CYP 3A4. Because macrolides inhibit this enzyme, concomitant administration of cisapride may cause the increase of QT interval prolongation, ventricular arrhythmias and torsades de pointes.
Cetirizine: In healthy volunteers, co-administration of a 5-day regimen of Azithromycin with cetirizine 20 mg at steady-state resulted in no pharmacokinetic interaction and no significant changes in the QT interval.
Didanosine (Dideoxyinosine): Co-administration of 1.2 g/day Azithromycin with 400 mg/day didanosine in 6 HIV positive subject did not appear to affect the steady-state pharmacokinetics of didanosine as compared with placebo.
Efavirenz: Co-administration of a 600 mg single dose of Azithromycin and 400 mg efavirenz daily for 7 days did not show any clinically significant pharmacokinetic interactions.

Store at temperature not exceeding 30°C. Protect from light.

Macrolides

J01FA10 - azithromycin ; Belongs to the class of macrolides. Used in the systemic treatment of infections.

Rx